Overview

This trial is active, not recruiting.

Condition cholinergic urticaria
Treatments active, placebo, open labeled
Phase phase 2
Sponsor Clinica Universidad de Navarra, Universidad de Navarra
Collaborator Hospital Clinic of Barcelona
Start date January 2014
End date September 2016
Trial size 24 participants
Trial identifier NCT02012387, CUN-OMAL-UCOL

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
Omalizumab 300 mg Subcutaneous route 300 mg dose (independent from total IgE, weight or high)
active Biological/Vaccine: Omalizumab
Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks
(Placebo Comparator)
Placebo Saline serum Subcutaneous route 0.6 ml saline serum with same volume as an active treatment
placebo Biological/Vaccine: Placebo
Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks
(Active Comparator)
After the double blinded period, all patients from both arms will receive the active drug for 8 more months.
open labeled Biological: Omalizumab
Two injections will be administered every four weeks for 8 months, we will administer 4 doses within 32 weeks

Primary Outcomes

Measure
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.

Secondary Outcomes

Measure
Quality of life
time frame: It will be evaluated up to 48 weeks.
Patients' card
time frame: It will be assessed up to 48 weeks.
Treatment drop offs in each sequence
time frame: Up to 48 weeks.

Eligibility Criteria

Male or female participants at least 14 years old.

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.

Additional Information

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
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, Immunoglobulin E (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 European Academy of Allergy and Clinical Immunology (EAACI), European Dermatology Forum (EDF) and urticaria network e.V (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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Clinica Universidad de Navarra, Universidad de Navarra.