Efficacy Study of Omalizumab in Cholinergic Urticaria

NCT ID: NCT02012387

Last Updated: 2019-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2017-06-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Cholinergic Urticaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Active

Omalizumab 300 mg Subcutaneous route 300 mg dose (independent from total IgE, weight or high)

Group Type ACTIVE_COMPARATOR

Active

Intervention Type BIOLOGICAL

Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks

Placebo

Placebo Saline serum Subcutaneous route 0.6 ml saline serum with same volume as an active treatment

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks

Open labeled

After the double blinded period, all patients from both arms will receive the active drug for 8 more months.

Group Type ACTIVE_COMPARATOR

Open labeled

Intervention Type BIOLOGICAL

Two injections will be administered every four weeks for 8 months, we will administer 4 doses within 32 weeks

Interventions

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Active

Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks

Intervention Type BIOLOGICAL

Placebo

Two injections will be administered every four weeks for four months, we will administer 4 doses within 16 weeks

Intervention Type BIOLOGICAL

Open labeled

Two injections will be administered every four weeks for 8 months, we will administer 4 doses within 32 weeks

Intervention Type BIOLOGICAL

Other Intervention Names

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Biological/Vaccine: Omalizumab Other Names: Xolair Biological/Vaccine: Placebo Other Names: Saline serum Biological: Omalizumab Other Names: Xolair

Eligibility Criteria

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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.
Minimum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Clinic of Barcelona

OTHER

Sponsor Role collaborator

Hospital Universitari Joan XXIII de Tarragona.

OTHER

Sponsor Role collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role collaborator

Complejo Hospitalario de Navarra

OTHER

Sponsor Role collaborator

Hospital Universitario Central de Asturias

OTHER

Sponsor Role collaborator

Hospital Clínico Universitario Lozano Blesa

OTHER

Sponsor Role collaborator

Hospital Vall d'Hebron

OTHER

Sponsor Role collaborator

Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Departamento de Alergología. Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Site Status

Countries

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Spain

References

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Morales AR, Shah N, Castells M. Antigen-IgE desensitization in signal transducer and activator of transcription 6-deficient mast cells by suboptimal doses of antigen. Ann Allergy Asthma Immunol. 2005 May;94(5):575-80. doi: 10.1016/S1081-1206(10)61136-2.

Reference Type BACKGROUND
PMID: 15945561 (View on PubMed)

Metz M, Altrichter S, Ardelean E, Kessler B, Krause K, Magerl M, Siebenhaar F, Weller K, Zuberbier T, Maurer M. Anti-immunoglobulin E treatment of patients with recalcitrant physical urticaria. Int Arch Allergy Immunol. 2011;154(2):177-80. doi: 10.1159/000320233. Epub 2010 Aug 24.

Reference Type BACKGROUND
PMID: 20733327 (View on PubMed)

Sabroe RA. Failure of omalizumab in cholinergic urticaria. Clin Exp Dermatol. 2010 Jun;35(4):e127-9. doi: 10.1111/j.1365-2230.2009.03748.x. Epub 2009 Nov 19.

Reference Type BACKGROUND
PMID: 19925484 (View on PubMed)

Baiardini I, Pasquali M, Braido F, Fumagalli F, Guerra L, Compalati E, Braga M, Lombardi C, Fassio O, Canonica GW. A new tool to evaluate the impact of chronic urticaria on quality of life: chronic urticaria quality of life questionnaire (CU-QoL). Allergy. 2005 Aug;60(8):1073-8. doi: 10.1111/j.1398-9995.2005.00833.x.

Reference Type BACKGROUND
PMID: 15969690 (View on PubMed)

Abajian M, Mlynek A, Maurer M. Physical urticaria. Curr Allergy Asthma Rep. 2012 Aug;12(4):281-7. doi: 10.1007/s11882-012-0269-0.

Reference Type BACKGROUND
PMID: 22653630 (View on PubMed)

Hirschmann JV, Lawlor F, English JS, Louback JB, Winkelmann RK, Greaves MW. Cholinergic urticaria. A clinical and histologic study. Arch Dermatol. 1987 Apr;123(4):462-7. doi: 10.1001/archderm.123.4.462.

Reference Type BACKGROUND
PMID: 3827277 (View on PubMed)

O'Donnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW. The impact of chronic urticaria on the quality of life. Br J Dermatol. 1997 Feb;136(2):197-201.

Reference Type BACKGROUND
PMID: 9068731 (View on PubMed)

Baiardini I, Giardini A, Pasquali M, Dignetti P, Guerra L, Specchia C, Braido F, Majani G, Canonica GW. Quality of life and patients' satisfaction in chronic urticaria and respiratory allergy. Allergy. 2003 Jul;58(7):621-3. doi: 10.1034/j.1398-9995.2003.00091.x.

Reference Type BACKGROUND
PMID: 12823121 (View on PubMed)

Tlougan BE, Mancini AJ, Mandell JA, Cohen DE, Sanchez MR. Skin conditions in figure skaters, ice-hockey players and speed skaters: part II - cold-induced, infectious and inflammatory dermatoses. Sports Med. 2011 Nov 1;41(11):967-84. doi: 10.2165/11592190-000000000-00000.

Reference Type BACKGROUND
PMID: 21985216 (View on PubMed)

Zuberbier T, Munzberger C, Haustein U, Trippas E, Burtin B, Mariz SD, Henz BM. Double-blind crossover study of high-dose cetirizine in cholinergic urticaria. Dermatology. 1996;193(4):324-7. doi: 10.1159/000246281.

Reference Type BACKGROUND
PMID: 8993958 (View on PubMed)

Nakamizo S, Egawa G, Miyachi Y, Kabashima K. Cholinergic urticaria: pathogenesis-based categorization and its treatment options. J Eur Acad Dermatol Venereol. 2012 Jan;26(1):114-6. doi: 10.1111/j.1468-3083.2011.04017.x. Epub 2011 Mar 4.

Reference Type BACKGROUND
PMID: 21371134 (View on PubMed)

Haas N, Toppe E, Henz BM. Microscopic morphology of different types of urticaria. Arch Dermatol. 1998 Jan;134(1):41-6. doi: 10.1001/archderm.134.1.41.

Reference Type BACKGROUND
PMID: 9449908 (View on PubMed)

Kozaru T, Fukunaga A, Taguchi K, Ogura K, Nagano T, Oka M, Horikawa T, Nishigori C. Rapid desensitization with autologous sweat in cholinergic urticaria. Allergol Int. 2011 Sep;60(3):277-81. doi: 10.2332/allergolint.10-OA-0269. Epub 2011 Feb 25.

Reference Type BACKGROUND
PMID: 21364312 (View on PubMed)

Gaig P, Olona M, Munoz Lejarazu D, Caballero MT, Dominguez FJ, Echechipia S, Garcia Abujeta JL, Gonzalo MA, Lleonart R, Martinez Cocera C, Rodriguez A, Ferrer M. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol. 2004;14(3):214-20.

Reference Type BACKGROUND
PMID: 15552715 (View on PubMed)

Other Identifiers

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CUN-OMAL-UCOL

Identifier Type: -

Identifier Source: org_study_id

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