Efficacy Study of Omalizumab in Cholinergic Urticaria (CUN-OMAL-UCOL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Clinica Universidad de Navarra, Universidad de Navarra
Sponsor:
Collaborators:
Hospital Clinic of Barcelona
Hospital Vall D'Hebrón, Barcelona
Hospital Joan XXIII, Tarragona
Hospital Gregorio Marañon, Madrid
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Hospital Basurto, Bilbao
Complejo Hospitalario de Navarra, Pamplona
Information provided by (Responsible Party):
Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier:
NCT02012387
First received: November 18, 2013
Last updated: January 18, 2014
Last verified: December 2013
  Purpose

To demonstrate the efficacy and safety of Omalizumab in a new indication, that is cholinergic urticaria.


Condition Intervention Phase
Cholinergic Urticaria
Biological: Active
Biological: Placebo
Biological: Open labeled
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multicenter Randomized, Double-blind, Placebo-controlled Parallel Clinical Trial to Assess Efficacy and Safety of Omalizumab (Xolair®) in a New Indication: Cholinergic Urticarial

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Negativization of the exercise challenge test [ Time Frame: It will be assessed prior to the study, and subsequently each 4 weeks up to 12 months. ] [ Designated as safety issue: No ]
    a. Our primary endpoint will be the negativization of the exercise challenge test: We will perform the exercise challenge test following the European Guidelines[14] for cholinergic urticaria. According with such guidelines, all centers will follow the same center standardized protocol. The patient will exercise in treadmill or running to the point of sweating and following for 15 more minutes, wearing warm clothing in a warm room. The test will be considered positive if exercise challenge leads to the typical rash over 10 minutes.


Secondary Outcome Measures:
  • Quality of life [ Time Frame: It will be evaluated up to 48 weeks. ] [ Designated as safety issue: No ]
    Quality of Life: QoL will be evaluated through the Spanish validated version of Chronic Urticaria quality of life (CU-Q2oL)

  • Patients' card [ Time Frame: It will be assessed up to 48 weeks. ] [ Designated as safety issue: Yes ]
    Use of medication, VAS, daily symptoms, emergency visits, days off work.

  • Treatment drop offs in each sequence [ Time Frame: Up to 48 weeks. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: January 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active
Omalizumab 300 mg Subcutaneous route 300 mg dose (independent from total IgE, weight or high)
Biological: Active
Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks
Other Names:
  • Biological/Vaccine: Omalizumab
  • Other Names:
  • Xolair
Placebo Comparator: Placebo
Placebo Saline serum Subcutaneous route 0.6 ml saline serum with same volume as an active treatment
Biological: Placebo
Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks
Other Names:
  • Biological/Vaccine: Placebo
  • Other Names: Saline serum
Active Comparator: Open labeled
After the double blinded period, all patients from both arms will receive the active drug for 8 more months.
Biological: Open labeled
Two injections will be administered every four weeks for 8 months, we will administer 4 doses within 32 weeks
Other Names:
  • Biological: Omalizumab
  • Other Names:
  • Xolair

Detailed Description:

Physical urticarias, such as delayed pressure, cholinergic, dermatographism and cold urticaria, are highly disabling conditions[1]. Cholinergic urticaria occurs due to an active (e.g. exercise) or passive (e.g. hot bath) increase in core body temperature, causing itching and small hives with flare reaction on the trunk and limps that fade away upon cooling of the body[2].

As it is the case of chronic urticaria, physical urticarias have a great impact on patients' quality of life[3, 4]. However, these types of urticarias cause even more alteration on quality of life because of the limitations they cause in daily life activities, sports practicing[5] or work performance.

In spite of the high morbidity of this disease and the impact on quality of life, there is no available treatment. Antihistamines that usually control other types of urticaria could only partially alleviate cholinergic urticaria. There is only one paper[6] that shows efficacy doubling the dose of cetirizine above the recommended dosage on the Summary of Product Characteristics (off-label dosage). The poor response to antihistamine is justified by the minimal role of histamine in its physiopathology and only after employing very high doses[7].

The etiology and pathogenesis of hive formation remains unknown, though it is recognized that mast cells are clearly involved[8]. On the other hand, it seems that desensitization or tolerance could be induced in cholinergic urticaria[9]. Thus as it is the case of drug desensitization, IgE receptor must also play a role in the development of this physical urticaria[10].

In the past years, the monoclonal humanized anti-IgE antibody (Omalizumab) was shown to be effective in control cholinergic urticaria[11] not respondent to conventional therapies at maximum or off-label doses. A negative response was also reported for cholinergic urticaria[12].

Our rationale for this approach in this type of urticaria is that Omalizumab exerts an inhibitory action on mast cell activation, as is the case of desensitization.

For that purpose, we will perform a multicenter, randomized, double-blind, placebo-controlled parallel clinical trial. We will include 24 patients including both female and male patients (age 14 years or older), non-respondent to antihistamines.

Efficacy will be evaluated through the negativization of the EAACI, EDF and UNEV standardized exercise challenge test, Visual Analog Scale (VAS), Chronic Urticaria Quality of Life validated questionnaire[13], patients' card of symptoms and use of rescue medication. Additional measures of efficacy will also be: the number of dropouts in each treatment group; the leave days due of urticaria and Emergency Department visits. Finally, safety will be assessed by means of recording and evaluation of adverse reactions during treatment.

As we previously stated, Omalizumab is not indicated for physical or other types of urticaria. The only indication is for treatment of moderate-to-severe allergic asthma. The hypothesis we are working on is that the monoclonal anti-IgE antibody Omalizumab could be as well effective in controlling physical urticaria symptoms in patients non-respondent to conventional therapy. We hypothesize that Omalizumab is able to revert the basophil or mast cell activation present in those urticaria types.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adult female and male patients (age 14 years or older). Diagnosis of cholinergic urticaria trough clinical history and positive challenge test.

Non-respondent to supra therapeutic doses of antihistamines (defined as 2x the maximal dose included in the drug labeling) Written informed consent.

Exclusion Criteria:

Pruritus related to dermatitis or other skin condition. Any systemic disease that hampers follow up or interpretation of data. Omalizumab treatment within the previous 12 months. Any exclusion criteria included in the drug labeling. Any other conditions that do not allow the accomplishment of the clinical trial requisites, such as the abuse of drugs or alcohol.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02012387

Contacts
Contact: Marta Ferrer Puga +34948255400 mferrerp@unav.es

Locations
Spain
Departamento de Alergología. Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Contact: Marta Ferrer Puga    +34 948255400    mferrerp@unav.es   
Principal Investigator: Marta Ferrer         
Sponsors and Collaborators
Clinica Universidad de Navarra, Universidad de Navarra
Hospital Clinic of Barcelona
Hospital Vall D'Hebrón, Barcelona
Hospital Joan XXIII, Tarragona
Hospital Gregorio Marañon, Madrid
Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Hospital Basurto, Bilbao
Complejo Hospitalario de Navarra, Pamplona
  More Information

Publications:

Responsible Party: Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier: NCT02012387     History of Changes
Other Study ID Numbers: CUN-OMAL-UCOL
Study First Received: November 18, 2013
Last Updated: January 18, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Keywords provided by Clinica Universidad de Navarra, Universidad de Navarra:
Cholinergic urticaria
Omalizumab

Additional relevant MeSH terms:
Urticaria
Omalizumab
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Allergic Agents
Therapeutic Uses
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 23, 2014