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Efficacy and Safety Study of Omalizumab (Xolair®) to Treat Chronic Urticaria

This study is currently recruiting participants.
Verified October 2012 by Clinica Universidad de Navarra, Universidad de Navarra
Sponsor:
Collaborators:
Hospital Clinic of Barcelona
Hospital de Basurto, Bilbao, Spain
Hospital Santiago Apostol, Vitoria-Gasteiz, Spain
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier:
NCT01713725
First received: October 22, 2012
Last updated: October 25, 2012
Last verified: October 2012
History of Changes
  Purpose

Chronic urticaria can be defined as the occurrence of widespread daily or almost daily wheals for at least 6 weeks, which may be accompanied by angioedema. While the wheals are transient, the resolution of angioedema is slower than wheals and could take up to 72 hours. The natural course of chronic urticaria is self-limited, with spontaneous remissions and occasional relapses. The investigators calculated a 0.6% (95% CI(Confidence Interval): 0.4-0.8) prevalence in a population study. It has a great impact on patients' quality of life. In a recent national survey on patients attending Allergy Department, chronic urticaria was the disease with greater impact on mental quality of life out of all allergic diseases.

In spite of the high morbidity of this disease and the impact in quality of life, there is no available treatment. Last guidelines recommend initiating treatment with antihistamine and if there is no response to increase the dose off-label up to four-fold; systemic corticosteroids are also recommended in short tapering and if no response, the only treatment with clinical evidence to be employed is cyclosporine. As additional data, the treatment cost of this disease has been calculated in 2047$/year.

In past years it has been employed the monoclonal humanized anti-Immunoglobulin IgE (iGE) antibody (Omalizumab) to treat moderate to severe asthma with good results. The rationale for this approach in chronic urticaria is that Omalizumab inhibits the binding of IgE to the high affinity IgE receptor (FceRI) which decreases the FceRI expression on the surface of mast cells and basophils so that immunoglobulin G cross linking of the alpha subunit and basophil degranulation is prevented.The hypothesis the investigators are working on is that monoclonal IgE antibody Omalizumab could be effective in controlling chronic urticaria symptoms in patients non respondent to conventional therapy. The investigators hypothesize that Omalizumab is able to revert the basophil or mast cell activation present in chronic urticaria.


Condition Intervention Phase
Chronic Urticaria
 Biological: Omalizumab
Biological: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter, Double- Blinded, Placebo- Controlled, Randomized, Cross-over (2x2) Clinical Trial, to Assess Efficacy and Safety of a New Indication for Omalizumab (Xolair®, Novartis) in Autoimmune and no Autoimmune Chronic Urticaria.

Resource links provided by NLM:

MedlinePlus related topics: Hives
Drug Information available for: Omalizumab
U.S. FDA Resources

Further study details as provided by Clinica Universidad de Navarra, Universidad de Navarra:

Primary Outcome Measures:
  • Symptom's control as measured by the UAS7 [ Time Frame: One year ] [ Designated as safety issue: No ]
    The Urticaria Activity Score 7 measures number the weekly average of hives and pruritus measured twice a day. It scores from 0 to 42


Secondary Outcome Measures:
  • Use of Medication [ Time Frame: One year ] [ Designated as safety issue: No ]
    Two antihistamines and corticosteroids are allowed as rescue medication that would be recorded by the patient.

  • Quality of life score (CU-Q2oL) [ Time Frame: One year ] [ Designated as safety issue: No ]
    Specific QOL score for chronic urticaria.It includes 23 items categorized under the following scales: limits looks, swelling/eating, functioning, sleep, mental status, and itching/embarrassment.


Other Outcome Measures:
  • Treatments drops off [ Time Frame: One year ] [ Designated as safety issue: No ]
    Number of patients that abandon the study due to lack of control of the disease

  • Days off [ Time Frame: One year ] [ Designated as safety issue: No ]
    Days off from work due to chronic urticaria symptoms


Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Omalizumab 300 mg
  • Subcutaneous route
  • 300 mg dose (independent from total IgE, weight or high)
 Biological: Omalizumab
  • Two injections will be administered the first two weeks
  • The following three injections will be administered every four weeks Consequently, we will administer 5 doses within 14 weeks
Other Name: Xolair
Biological: Placebo
  • Two injections will be administered the first two weeks
  • The following three injections will be administered every four weeks Consequently, we will administer 5 doses within 14 weeks
Other Name: Saline serum
Placebo Comparator: Placebo
  • Saline serum
  • Subcutaneous route
  • 0.6 ml saline serum with same volume as an active treatment
 Biological: Omalizumab
  • Two injections will be administered the first two weeks
  • The following three injections will be administered every four weeks Consequently, we will administer 5 doses within 14 weeks
Other Name: Xolair
Biological: Placebo
  • Two injections will be administered the first two weeks
  • The following three injections will be administered every four weeks Consequently, we will administer 5 doses within 14 weeks
Other Name: Saline serum

Detailed Description:

The objective of the present study is to demonstrate with an adequate methodology the efficacy and safety of Omalizumab for a new indication that is chronic autoimmune and no autoimmune urticaria. For that purpose, The investigators will perform a Multicenter double- blinded, placebo- controlled, randomized cross-over (2x2) trial. The investigators will include 40 patients (ten per collaborative center) including both female and male adults non respondent to antihistamines at supra therapeutic dose. Efficacy will be evaluated through the Urticaria Activity Score 7 (UAS7), Chronic Urticaria Quality of Life validated questionnaire, patients' symptoms card and use of medication. Dropouts in each treatment group will be also evaluated. The investigators will also record leave days because of urticaria and Emergency Department visits, as well as adverse reactions during treatment.

The present study would allow to offer to the Health System an evidence to evaluate the convenience or not to approve the use of Omalizumab for the new indication of chronic urticaria treatment. It is important to take into account that in the present study the investigators will include both autoimmune and non-autoimmune urticaria, since the efficacy could differ between both urticaria types. In the same way, the Health Authorities (AEMPS) would have independent additional information obtained through adequate methodology in the case that a new indication is requested. The investigators also want to stress that in the near future the company that manufactures this antibody could ask for a new indication for chronic urticaria.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult female and male patients
  • Diagnosis of chronic autoimmune or non autoimmune urticaria
  • The investigators defined chronic urticarial as the occurrence of widespread daily or almost daily wheals for at least 6 weeks, which may be accompanied by angioedema. While the wheals are transient, the resolution of angioedema is slower than wheals and could take up to 72 hours.
  • No response to therapeutic doses of antihistamines
  • The investigators define therapeutic doses of antihistamines the maximal dose included in the drug labeling
  • Written informed consent.

Exclusion Criteria:

  • Urticaria vasculitis or any kind of physical urticaria
  • Total IgE value above 700 UI/l
  • Pruritus related to dermatitis or other skin condition
  • Any systemic disease that do not allow to follow up or interpretation data
  • Omalizumab treatment within the previous 12 months
  • Treatment with corticosteroids or immunosuppressive drugs within the previous 4 weeks
  • Any exclusion criteria included in the drug labeling
  • Any other condition that do not allow to accomplish the clinical trial requisites as use of drugs, alcohol.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01713725

Contacts
Contact: Marta Ferrer, MD, PhD +34948255400 ext 4456 mferrerp@unav.es

Locations
Spain
Hospital Santiago Apostol Recruiting
Vitoria, Alava, Spain, 01004
Contact: Daniel Muñoz Lejarazu, MD     +34945007754     dlejarazu@hsan.osakidetza.net    
Principal Investigator: Daniel Muñoz Lejarazu, MD            
Sub-Investigator: Maite Audicana, MD, PhD            
Clinica Universitaria de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Contact: Marta Ferrer, MD, PhD     +34948255400 ext 4456     mferrerp@unav.es    
Sub-Investigator: Gabriel Gastaminza, MD, PhD            
Sub-Investigator: Jaime deAlgorta, MD, PhD, MPH            
Sub-Investigator: Claude Michel Urbain, MD            
Hospital de Basurto Recruiting
Bilbao, Vizvaya, Spain, 48013
Contact: Pedro Gamboa, MD, PhD     690139855     pmgamboa@telefonica.net    
Sub-Investigator: Pedro Gamboa, MD, PhD            
Principal Investigator: Ignacio Antepara, MD            
Hospital Clinic Recruiting
Barcelona, Spain, 08036
Contact: Antonio Valero, MD         valero@clinic.ub.es    
Sub-Investigator: Joan Bartra, MD            
Principal Investigator: Antonio Valero, MD            
Sponsors and Collaborators
Clinica Universidad de Navarra, Universidad de Navarra
Hospital Clinic of Barcelona
Hospital de Basurto, Bilbao, Spain
Hospital Santiago Apostol, Vitoria-Gasteiz, Spain
Investigators
Principal Investigator: Marta Ferrer, MD, PhD Clinica Universitaria, Universidad de Navarra
  More Information

Publications:

Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier: NCT01713725     History of Changes
Other Study ID Numbers: CUN-OMAL-CU-2010, 2010-024113-31
Study First Received: October 22, 2012
Last Updated: October 25, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra:
Chronic urticaria
Chronic spontaneous urticaria
Autoimmune and non autoimmune urticaria
UAS7

Additional relevant MeSH terms:
Urticaria
Omalizumab
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
 Immune System Diseases
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on June 18, 2013