Chronic UrticariaPhase 2NCT01713725
Efficacy and Safety Study of Omalizumab (Xolair®) to Treat Chronic Urticaria
A Phase 2 study testing Omalizumab in people with Chronic Urticaria, run by Clinica Universidad de Navarra, Universidad de Navarra at 4 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Urticaria
- What is being tested?
- Omalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 4 sitesSpain
- Study dates
- Mar 2012to Jun 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
Spain4 sites
Hospital Clinic
Barcelona, 08036
Hospital de Basurto
Bilbao, Vizvaya, 48013
Clinica Universitaria de Navarra
Pamplona, Navarre, 31008
Hospital Santiago Apostol
Vitoria-Gasteiz, Alava, 01004
About this study
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.
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.
Read the 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 20 patients 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.
A third outcome expected is to offer information on the lasting effect of the drug that is symptoms' free weeks after the dose. This information would be provided from the washing period data and from those patients who were allocated of placebo after the active drug arm. This would give much needed information on the best dosing scheduling protocol.
- Conditions
- Chronic Urticaria
- Being tested
- Omalizumab, Placebo
- Keywords
- Chronic urticaria, Chronic spontaneous urticaria, Autoimmune and non autoimmune urticaria, UAS7
- Medical subject headings
- Chronic Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmalizumabBiological
Also called Xolair
- 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
PlaceboBiological
Also called Saline serum
- 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
| Study group | Role | What they receive |
|---|---|---|
| Omalizumab 300 mg | Active comparator | * Subcutaneous route
* 300 mg dose (independent from total IgE, weight or high) Receives: Biological: Omalizumab; Biological: Placebo |
| Placebo | Placebo comparator | * Saline serum
* Subcutaneous route
* 0.6 ml saline serum with same volume as an active treatment Receives: Biological: Omalizumab; Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptom's control as measured by the UAS7
The Urticaria Activity Score 7 measures number the weekly average of hives and pruritus measured twice a day. It scores from 0 to 42
Measured: One year
Secondary outcomes (2)
Use of Medication
Two antihistamines and corticosteroids are allowed as rescue medication that would be recorded by the patient.
Measured: One year
Quality of life score (CU-Q2oL)
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2012 (estimated)
- Study startMar 2012
- Primary completionFeb 2016
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic UrticariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinica Universidad de Navarra, Universidad de Navarra
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Clinic of Barcelona, Hospital Universitario Central de Asturias, Gregorio Marañón Hospital, Hospital Universitari Joan XXIII de Tarragona., Complejo Hospitalario de Navarra, Hospital Vall d'Hebron, Hospital Clínico Universitario Lozano Blesa
- Responsible party
- Sponsor
- Investigators
- Marta Ferrer, MD, PhD, Principal investigator, Clinica Universitaria, Universidad de Navarra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713725
- Sponsor's protocol ID
- CUN-OMAL-CU-2010
- Other IDs
- 2010-024113-31
- Status last verified
- Apr 2017
- First submitted
- 22 Oct 2012
- Last updated
- 24 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Ferrer M, Gamboa P, Sanz ML, Goikoetxea MJ, Cabrera-Freitag P, Javaloyes G, Berroa F, Kaplan AP. Omalizumab is effective in nonautoimmune urticaria. J Allergy Clin Immunol. 2011 May;127(5):1300-2. doi: 10.1016/j.jaci.2010.12.1085. Epub 2011 Feb 11. No abstract available.
PubMed 21315432Gaig 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.
PubMed 15552715Ferrer M. Epidemiology, healthcare, resources, use and clinical features of different types of urticaria. Alergologica 2005. J Investig Allergol Clin Immunol. 2009;19 Suppl 2:21-6.
PubMed 19530414Mathias SD, Crosby RD, Zazzali JL, Maurer M, Saini SS. Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2012 Jan;108(1):20-24. doi: 10.1016/j.anai.2011.09.008. Epub 2011 Nov 2.
PubMed 22192960Saini S, Rosen KE, Hsieh HJ, Wong DA, Conner E, Kaplan A, Spector S, Maurer M. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011 Sep;128(3):567-73.e1. doi: 10.1016/j.jaci.2011.06.010. Epub 2011 Jul 18.
PubMed 21762974Valero A, Herdman M, Bartra J, Ferrer M, Jauregui I, Davila I, del Cuvillo A, Montoro J, Mullol J, Sastre J, Canonica GW, Baiardini I. Adaptation and validation of the Spanish version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL). J Investig Allergol Clin Immunol. 2008;18(6):426-32.
PubMed 19123433
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01713725
- Acronym / sponsor ID
- CUN-OMAL-CU-2010
- Conditions
- Chronic Urticaria
- Keywords
- Chronic urticaria, Chronic spontaneous urticaria, Autoimmune and non autoimmune urticaria, UAS7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Clinica Universidad de Navarra, Universidad de NavarraUniversity, hospital or other
- Collaborators
- Hospital Clinic of Barcelona, Hospital Universitario Central de Asturias, Gregorio Marañón Hospital, Hospital Universitari Joan XXIII de Tarragona., Complejo Hospitalario de Navarra, Hospital Vall d'Hebron, Hospital Clínico Universitario Lozano Blesa
- Study start
- Mar 2012 (actual)
- Primary completion
- Feb 2016 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 25 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 20 patients 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.
A third outcome expected is to offer information on the lasting effect of the drug that is symptoms' free weeks after the dose. This information would be provided from the washing period data and from those patients who were allocated of placebo after the active drug arm. This would give much needed information on the best dosing scheduling protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Omalizumab 300 mg | Active comparator | Biological: Omalizumab, Biological: Placebo* Subcutaneous route * 300 mg dose (independent from total IgE, weight or high) |
| Placebo | Placebo comparator | Biological: Omalizumab, Biological: Placebo* Saline serum * Subcutaneous route * 0.6 ml saline serum with same volume as an active treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OmalizumabAlso: Xolair* 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 | Biological | Omalizumab 300 mg, Placebo |
| PlaceboAlso: Saline serum* 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 | Biological | Omalizumab 300 mg, Placebo |
Primary outcome
Symptom's control as measured by the UAS7
Time frame: One year
The Urticaria Activity Score 7 measures number the weekly average of hives and pruritus measured twice a day. It scores from 0 to 42
2 secondary outcomes
Use of Medication
Time frame: One year
Quality of life score (CU-Q2oL)
Time frame: One year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2017.
- Background: PubMed 21315432Ferrer M, Gamboa P, Sanz ML, Goikoetxea MJ, Cabrera-Freitag P, Javaloyes G, Berroa F, Kaplan AP. Omalizumab is effective in nonautoimmune urticaria. J Allergy Clin Immunol. 2011 May;127(5):1300-2. doi: 10.1016/j.jaci.2010.12.1085. Epub 2011 Feb 11. No abstract available.
- Background: PubMed 15552715Gaig 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.
- Background: PubMed 19530414Ferrer M. Epidemiology, healthcare, resources, use and clinical features of different types of urticaria. Alergologica 2005. J Investig Allergol Clin Immunol. 2009;19 Suppl 2:21-6.
- Background: PubMed 22192960Mathias SD, Crosby RD, Zazzali JL, Maurer M, Saini SS. Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2012 Jan;108(1):20-24. doi: 10.1016/j.anai.2011.09.008. Epub 2011 Nov 2.
- Background: PubMed 21762974Saini S, Rosen KE, Hsieh HJ, Wong DA, Conner E, Kaplan A, Spector S, Maurer M. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011 Sep;128(3):567-73.e1. doi: 10.1016/j.jaci.2011.06.010. Epub 2011 Jul 18.
- Background: PubMed 19123433Valero A, Herdman M, Bartra J, Ferrer M, Jauregui I, Davila I, del Cuvillo A, Montoro J, Mullol J, Sastre J, Canonica GW, Baiardini I. Adaptation and validation of the Spanish version of the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL). J Investig Allergol Clin Immunol. 2008;18(6):426-32.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marta Ferrer, MD, PhD principal investigator
Clinica Universitaria, Universidad de Navarra
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omalizumab in people with Chronic Urticaria, run by Clinica Universidad de Navarra, Universidad de Navarra at 4 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symptom's control as measured by the UAS7 (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01713725, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2017.